1. Field of the Invention
The present invention provides a method of isolation, characterization and artificial differentiation of in vitro adult human germ cells.
2. Description of the Background
Over the years, culture conditions for mouse spermatogonial stem cells (SSCs) have been established, facilitating the characterization of these cells and factors involved in self-renewal and differentiation. Nonetheless, several lines of evidence suggested that the ability to derive pluripotent germ cell lines was restricted to the earliest stages of development (to PGCs) and that pluripotency of germ cells was not maintained postnatally. However, recent results from mice have challenged this assumption. The pluripotency of mouse spermatogonia-derived stem cells termed mGSCs (multipotent germline stem cells), maGSCs (multipotent adult germline stem cells) or MACS (multipotent adult spermatogonial-derived stem cells) has been demonstrated by several criteria including ability to spontaneously differentiate into derivatives of the three primary germ layers and to contribute to chimeras. Notably, elegant studies in mice have resulted in the identification of the progenitor population and delineation of the time course of acquisition of pluripotency.
Since publication of these mice studies, research has been directed toward duplicating these findings in vitro with human spermatogonial stem cells. If reproducible in humans, these findings would identify the testicle as a source of multipotent or even pluripotent stem cells that might be used for patient-specific, non-embryo derived, stem cell-based therapy in the future. It would also suggest the possibility of differentiating testis stem cells to more mature, haploid forms and even to sperm.
Germ cell maturation has proven to be a difficult task in the laboratory. This has precluded the in vitro maturation of early human germ cells to mature sperm. The development of mature sperm would provide new therapies for men who have been rendered sterile for various reasons, including cancer treatment. It would also provide an in vitro construct to study the biology of spermatogenesis and the effects of reproductive toxins and drugs in sperm production. Thus, a need for a method of maturing early human germ cells to mature sperm continues to exist.